Neuropsychological profile of French adults with early-treated phenylketonuria: a multicenter study.

Background And Objective: Adult patients with early-treated phenylketonuria (AwET-PKU) may present some subtle neurocognitive deficits. The aim of the study was to investigate 1) neurocognitive functions in a large group of AwET-PKU 2) the influence of plasma phenylalanine (Phe).

Methods: Participants: 187 AwET-PKU (classic PKU [cPKU] 81%, mild PKU [mPKU] 14%, and mild persistent hyperphenylalaninemia [MPH] 5%).

Pro-angiogenic changes of T-helper lymphocytes in hereditary hemorrhagic telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) is a rare inherited disease due to heterozygous loss-of-function mutations on the BMP9/10 pathway ( or mainly). HHT endothelial cells are prone to lose their quiescence, leading to progressive appearance of numerous telangiectases on skin and mucosa (complicated by epistaxis and anemia), and to larger arteriovenous malformations in lungs, liver and brain. HHT is also associated with T lymphocyte abnormalities, which are currently poorly understood.

Impact of mutation on aggressiveness and outcomes in adult clonal histiocytosis.

Histiocytoses encompass a wide spectrum of diseases, all characterized by tissue infiltration by CD68+ histiocytes. Most adult histiocytoses are considered clonal diseases because they highlight recurrent somatic mutations in the MAP-kinase pathway gene, primarily . The presence of mutation is associated with widespread disease in children with Langerhans cell histiocytosis (LCH) or cardiovascular/neurological involvement in Erdheim-Chester disease (ECD).

Antiplatelet and anticoagulant therapies in hereditary hemorrhagic telangiectasia: A large French cohort study (RETROPLACOTEL).

Background: It is unclear whether hereditary hemorrhagic telangiectasia (HHT) patients can tolerate antithrombotic therapies (AT) including antiplatelet (AP) and/or anticoagulant (AC) agents.

Objectives: Primary endpoint was tolerance to AT in HHT. Secondary endpoints were to identify factors associated with major bleeding events (MBE) and premature discontinuation of AT.

Development and validation of a quality of life measurement scale specific to hereditary hemorrhagic telangiectasia: the QoL-HHT.

Background: Hereditary hemorrhagic telangiectasia (HHT) disease is a rare genetic disorder with symptoms and complications that can significantly affect patients' daily lives. To date, no scale has been validated to assess the specific symptoms of this disease on the quality of life (QOL) of HHT patients. This makes it difficult for clinicians to accurately measure the quality of life of patients with HHT.

Sphingosine-1-Phosphate Levels Are Higher in Male Patients with Non-Classic Fabry Disease.

Fabry disease is an X-linked lysosomal disease in which defects in the alpha-galactosidase A enzyme activity lead to the ubiquitous accumulation of glycosphingolipids. Whereas the classic disease is characterized by neuropathic pain, progressive renal failure, white matter lesions, cerebral stroke, and hypertrophic cardiomyopathy (HCM), the non-classic phenotype, also known as cardiac variant, is almost exclusively characterized by HCM. Circulating sphingosine-1-phosphate (S1P) has controversially been associated with the Fabry cardiomyopathy.

Challenging the traditional approach for interpreting genetic variants: Lessons from Fabry disease.

Fabry disease (FD) is an X-linked genetic disease due to pathogenic variants in GLA. The phenotype varies depending on the GLA variant, alpha-galactosidase residual activity, patient's age and gender and, for females, X chromosome inactivation. Over 1000 variants have been identified, many through screening protocols more susceptible to disclose non-pathogenic variants or variants of unknown significance (VUS).

A Cross-Sectional Retrospective Study of Non-Splenectomized and Never-Treated Patients with Type 1 Gaucher Disease.

Patients with type 1 Gaucher disease (GD1) present thrombocytopenia, anemia, organomegaly, and bone complications. Most experts consider that the less aggressive forms do not require specific treatment. However, little is known about the disease course of these forms.

Cornea verticillata and acroparesthesia efficiently discriminate clusters of severity in Fabry disease.

Backgroud: Fabry disease (OMIM #301 500), the most prevalent lysosomal storage disease, is caused by enzymatic defects in alpha-galactosidase A (GLA gene; Xq22.1). Fabry disease has historically been characterized by progressive renal failure, early stroke and hypertrophic cardiomyopathy, with a diminished life expectancy.

Coagulation Parameters in Adult Patients With Type-1 Gaucher Disease.

Background: Gaucher disease is a rare inborn error of lysosomal metabolism, characterized by lysosomal storage of the β-glucosylceramide. Bleedings observed in type-1 Gaucher disease (GD1) are commonly attributed to a low platelet count, but they can also occur when the platelet count is normal or slightly low. Abnormal platelet function has been described and deficiencies in coagulation factors too, such as factors II, V, VII, VIII, IX, X, XI, XII, and von Willebrand factor.

Splenic Artery Aneurysms, A Rare Complication of Type 1 Gaucher Disease: Report of Five Cases.

Type 1 Gaucher disease is a rare genetic lysosomal disorder due to acid betaglucosidase deficiency. The main features are thrombocytopenia, anemia, hepatosplenomegaly and complex skeletal disease. Complications include pulmonary hypertension, cirrhosis and splenic infarction; comorbidities, such as autoimmune phenomena, B-cell malignancies and Parkinson disease also occur.

Venous thromboembolic events during warm autoimmune hemolytic anemia.

Thrombotic manifestations are a hallmark of many auto-immune diseases (AID), specially of warm autoimmune hemolytic anemia (wAIHA), as 15 to 33% of adults with wAIHA experience venous thromboembolic events (VTE). However, beyond the presence of positive antiphospholipid antibodies and splenectomy, risk factors for developing a VTE during wAIHA have not been clearly identified. The aim of this retrospective study was to characterize VTEs during wAIHA and to identify risk factors for VTE.

Diagnosis of hyperferritinemia in routine clinical practice.

The discovery of hyperferritinemia is often fortuitous, revealed in results from a laboratory screening or follow-up test. The aim of the diagnostic procedure is therefore to identify its cause and to identify or rule out hepatic iron overload, in a three-stage process. In the first step, clinical findings and several simple laboratory tests are sufficient to detect four of the most frequent causes of high ferritin concentrations: alcoholism, inflammatory syndrome, cytolysis, and metabolic syndrome.

Efficacy and safety of dapsone as second line therapy for adult immune thrombocytopenia: A retrospective study of 42 patients.

Dapsone is recommended as a second line therapy in immune thrombocytopenia (ITP), but is underused because of its potential side effects. The medical charts of 42 ITP patients treated with dapsone (100 mg/day) were retrospectively reviewed in order to assess its efficacy and safety in daily clinical practice. The overall response rate was 54.

Pulmonary hypertension subtypes associated with hereditary haemorrhagic telangiectasia: Haemodynamic profiles and survival probability.

Background: Different pulmonary hypertension (PH) mechanisms are associated with hereditary haemorrhagic telangiectasia (HHT).

Methods And Results: We conducted a retrospective study of all suspected cases of PH (echocardiographically estimated systolic pulmonary artery pressure [sPAP] ≥ 40 mmHg) in patients with definite HHT recorded in the French National Reference Centre for HHT database. When right heart catheterization (RHC) was performed, PH cases were confirmed and classified among the PH groups according to the European guidelines.

B cell depleting therapy regulates splenic and circulating T follicular helper cells in immune thrombocytopenia.

B cells are involved in immune thrombocytopenia (ITP) pathophysiology by producing antiplatelet auto-antibodies. However more than a half of ITP patients do not respond to B cell depletion induced by rituximab (RTX). The persistence of splenic T follicular helper cells (TFH) that we demonstrated to be expanded during ITP and to support B cell differentiation and antiplatelet antibody-production may participate to RTX inefficiency.

Etiologies and prognostic factors of leukocytoclastic vasculitis with skin involvement: A retrospective study in 112 patients.

In this study, outcomes of patients with leukocytoclastic vasculitis (LCV) were analyzed focusing on clinical, histopathology and laboratory findings, relapses, and survival.Data from patients with cutaneous vasculitis diagnosed between January 1, 2000, and December 31, 2010, at Dijon University Hospital (France) were retrospectively reviewed. LCV was defined as perivascular neutrophilic infiltrate, endothelial cell nuclear swelling, extravasation of red blood cells, and/or fibrin deposition in vessels.

Dose - response relationship of bevacizumab in hereditary hemorrhagic telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT), a genetic vascular disorder associated with epistaxis and hepatic shunts, is responsible for high-output cardiac failure in rare cases. Bevacizumab, which targets vascular endothelial growth factor, was shown to decrease both cardiac index (CI) and epistaxis duration in HHT patients with severe liver involvement. The relationship between its serum concentration and change in both CI and epistaxis duration was investigated to design the bevacizumab maintenance dosing regimen of future therapeutic studies.

Splenic TFH expansion participates in B-cell differentiation and antiplatelet-antibody production during immune thrombocytopenia.

Antiplatelet-antibody-producing B cells play a key role in immune thrombocytopenia (ITP) pathogenesis; however, little is known about T-cell dysregulations that support B-cell differentiation. During the past decade, T follicular helper cells (TFHs) have been characterized as the main T-cell subset within secondary lymphoid organs that promotes B-cell differentiation leading to antibody class-switch recombination and secretion. Herein, we characterized TFHs within the spleen of 8 controls and 13 ITP patients.